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Titolo:
Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease
Autore:
Bezard, E; Dovero, S; Prunier, C; Ravenscroft, P; Chalon, S; Guilloteau, D; Crossman, AR; Bioulac, B; Brotchie, JM; Gross, CE;
Indirizzi:
Univ Bordeaux 2, Neurophysiol Lab, CNRS, Unite Mixte Rech 5543,Basal Gang,F-33076 Bordeaux, France Univ Bordeaux 2 Bordeaux France F-33076 al Gang,F-33076 Bordeaux, France Univ Manchester, Sch Biol Sci, Div Neurosci, Manchester Movement Disorder Lab, Manchester M13 9PT, Lancs, England Univ Manchester Manchester Lancs England M13 9PT M13 9PT, Lancs, England INSERM, U316, Lab Biophys Med & Pharmaceut, F-37200 Tours, France INSERM Tours France F-37200 phys Med & Pharmaceut, F-37200 Tours, France Motac Neurosci Ltd, Manchester, Lancs, England Motac Neurosci Ltd Manchester Lancs England , Manchester, Lancs, England
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 17, volume: 21, anno: 2001,
pagine: 6853 - 6861
SICI:
0270-6474(20010901)21:17<6853:RBTAOS>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
MPTP-INDUCED PARKINSONISM; MONKEY MACACA-FASCICULARIS; MESSENGER-RNA LEVELS; SUBSTANTIA-NIGRA; DOPAMINE TRANSPORTER; HUMAN-BRAIN; RECEPTOR SUPERSENSITIVITY; STRIATAL PREPROENKEPHALIN; COMPENSATORY MECHANISMS; DIFFERENTIAL REGULATION;
Keywords:
threshold for symptom appearance; early D-2 dopaminergic receptor upregulation; substantia nigra; striatum; dopaminergic homeostasis; compensatory mechanisms;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
69
Recensione:
Indirizzi per estratti:
Indirizzo: Bezard, E Univ Bordeaux 2, Neurophysiol Lab, CNRS, Unite Mixte Rech 5543,Basal Gang,146 Rue Leo Seignat, F-33076 Bordeaux, France Univ Bordeaux 2 146Rue Leo Seignat Bordeaux France F-33076 nce
Citazione:
E. Bezard et al., "Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease", J NEUROSC, 21(17), 2001, pp. 6853-6861

Abstract

The concept of a threshold of dopamine (DA) depletion for onset of Parkinson's disease symptoms, although widely accepted, has, to date, not been determined experimentally in nonhuman primates in which a more rigorous definition of the mechanisms responsible for the threshold effect might be obtained. The present study was thus designed to determine (1) the relationship between Parkinsonian symptom appearance and level of degeneration of the nigrostriatal pathway and (2) the concomitant presynaptic and postsynaptic striatal response to the denervation, in monkeys treated chronically with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine according to a regimen that produces a progressive Parkinsonian state. The kinetics of the nigrostriatal degeneration described allow the determination of the critical thresholds associated to symptom appearance, these were a loss of 43.2% of tyrosine hydroxylase-immunopositive neurons at the nigral level and losses of 80.3 and 81.6% DA transporter binding and DA content, respectively, at the striatal level. Our data argue against the concept that an increase in DA metabolism could act as an efficient adaptive mechanism early in the disease progress. Surprisingly, the D-2-like DA receptor binding showed a biphasic regulation in relation to the level of striatal dopaminergic denervation, i.e., an initial decrease in the presymptomatic period was followed by an upregulation of postsynaptic receptors commencing when striatal dopaminergic homeostasis is broken. Further in vivo follow-up of the kinetics of striatal denervation in this, and similar, experimental models is now needed with a view to developing early diagnosis tools and symptomatic therapies that might enhanceendogenous compensatory mechanisms.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/06/19 alle ore 17:47:56